Studies are proposed in Part I to determine the influence of the enteric nervous system on the transport of electrolytes and water by the small and large intestine of rabbit. Previous studies have shown that stimulation of the enteric nerves (probably submucous neurons) reduces chloride absorption in human ileum and sigmoid colon, and causes secretion of chloride in jejunum and cecum. Tests of 3 hypotheses will be continued: 1) Stimuli (chemical or mechanical) that evoke changes in transport do so, in part, through enteric neural reflexes; 2) By means of such reflexes, some mucosal stimuli can alter ion and fluid transport at sites remote from the site of stimulation; and 3) A response in ion transport will differ depending upon whether the segment studied is orad or aborad from the stimulated segment. The stimuli to be studied are mechanical (distension) and chemical (bile salts, serotonin, E. coli ST toxin and theophylline). Transport will be studied by standard methods in anesthetized rabbits and by measuring ion fluxes and electrical indices in a specially-designed flux chamber. In part II, we will determine whether the effects of peptides on transport by the mucosa of the human small and large intestine are mediated directly by receptors on enterocytes, or indirectly by release of secondary neurotransmitters. Peptides that are present in varicosities or nerve endings arising from fibers of the myenteric plexus will be studied because of their probable physiological relevance. In tissues obtained at surgery, stripped of muscularis propria and mounted in a standard flux chamber, we will asssess the neural mediation by determining whether the short-circuit current change induced by the peptide is reduced with the neurotoxin, tetrodotoxin. If it is, we will try to identify the transmitter with specific antagonists, e.g., atropine, putative VIP antagonists, or by desensitization. Such studies should complement studies of transmitter release monitored immunochemically (by others) by demonstrating a biological effect of such release. Study of human tissues is required because of species variability.